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Biomedical subjects

B J Kemler

Publications and source records attributed to B J Kemler.

6 recordsLinked to original sources

Persistent non-A, non-B hepatitis in experimentally infected chimpanzees.

Non-A, non-B (NANB) hepatitis was transmitted to six chimpanzees by intravenous inoculation of antihemophilic (factor VIII) materials, acute-phase chimpanzee liver, and chronic-phase plasma obtained from two NANB hepatitis-infected chimpanzees 10 and 16 months, respectively, after their inoculation. Five of six experimentally infected chimpanzees observed for more than one year demonstrated persistent or intermittent elevations in levels of serum alanine aminotransferase (ALT) indicative of continuing liver dysfunction. Liver biopsy specimens obtained from three chimpanzees with persistent elevations in levels of ALT were positive for hepatocyte cytoplasmic structures associated with NANB hepatitis for as long as 27 months after inoculation. Liver biopsy specimens obtained from four infected animals 13-30 months after inoculation also showed mild but persistent histopathologic lesions of undefined character. The detection of circulating immune complexes in one chimpanzee with persistent elevations in levels of ALT suggests that these complexes may be involved in the pathogenesis of NANB hepatitis.

Animals↗

Inflammatory bowel disease associated circulating immune complexes.

Circulating immune complexes have been detected in patients with inflammatory bowel disease (IBD). To determine if these complexes are related specificially to IBD or more generally to loss of intestinal mucosal integrity, we compared circulating immune complex levels in the sera of 86 IBD patients, nine pseudomembranous and nine bacterial colitis patients, and 42 healthy controls. Immune complexes were measured by a Raji cell radioimmunoassay. Raji detectable circulating immune complex levels were significantly higher in the IBD group than in the healthy controls (P<0.001). Circulating immune complex levels in the pseudomembranous-bacterial colitis group and the healthy controls were essentially identical. While nearly 20% of the IBD patients (16 of 86) had abnormally high levels, none of the patients with the other forms of intestinal inflammation (0 of 18) had abnormal levels. These data suggest that the circulating immune complexes present in inflammatory bowel disease patients are related to the IBD process rather than to non-specific mucosal cell (barrier) damage. Patients with intestinal inflammation and normal peripheral immune complex levels also had normal mesenteric vein levels. These data suggest that lack of formation, rather than more efficient hepatic reticuloendothelial clearance, was primarily responsible for the absence of detectable complexes in Raji negative individuals. Circulating immune complex levels did not correlate with type, location, severity, or extraintestinal manifestations of inflammatory bowel disease. The absence of Raji detectable circulating immune complexes in the majority of patients, even in those with extraintestinal manifestations, raises serious doubts about the pathogenic significance of such complexes. Nevertheless, as the circulating immune complexes appear to be disease related, they may be used to isolate and identify disease specific antigen(s) of possible aetiological importance.

Antigen-Antibody Complex↗

Inflammatory bowel disease: study of cell mediated cytotoxicity for isolated human colonic epithelial cells.

A better understanding of the mechanism(s) of cell mediated toxicity for colon cells in vitro may help clarify the pathogenesis of inflammatory bowel disease (IBD). We have examined both the cytotoxicity of IBD peripheral blood mononuclear cells and the kinetics of induction of such toxicity by soluble plasma factors. Peripheral blood mononuclear cells from IBD patients were found to be cytotoxic for the colon cells. With the use of Chang cells, this cytotoxicity was shown not to be due to an increase in spontaneous cell mediated cytotoxicity. Colon cell toxicity in vitro did not correlate with site of disease or severity, but decreased toxicity appeared to be associated with in vivo steroid administration. Plasma from some IBD patients was capable of inducing normal peripheral blood mononuclear cells to be toxic to colon cells. This ability was not affected by steroid therapy. The induction capacity of IBD plasma was not associated with the presence of circulating immune complexes, as measured by Raji RIA, suggesting that large complement fixing complexes are not the inducing and directing factors. Unlike findings in other systems, induction could be demonstrated after a one hour preincubation of mononuclear cells with IBD plasma. The kinetics of induction are consistent with the hypothesis that either cytophilic antibody or small circulating immune complexes arm K cells for specific colon cell lysis.

Antigen-Antibody Complex↗

Immune regulation in inflammatory bowel disease: absence of a serum inhibitor of suppressor cell function.

Suppressor cell function of normal peripheral blood mononuclear cells was unaltered by preincubation with sera from patients with severe inflammatory bowel disease (IBD). These results suggest that, in contrast to juvenile rheumatoid arthritis and systemic lupus erythematosus, the decreased suppressor cell activity in IBD is not mediated by anti-suppressor cell antibodies.

Antibody Formation↗

Failure to detect circulating immune complexes in allergic patients on injection therapy.

Injection therapy for allergic diseases may create an environment conducive to circulating immune complex formation. Therefore, we examined the sera of eleven patients receiving injection therapy for the presence of circulating immune complexes. A sensitive Raji cell radioimmune assay was used to examine the sera prior to and 4, 8 and 24 hours after allergenic injection. Levels measured in these sera were compared to values obtained from forty-two healthy controls. Ten of eleven allergic patients receiving injection therapy had values within the normal range prior to maintenance injection. These ten patients also had normal values for circulating immune complexes at each interval after maintenance injection. The data suggest that circulating immune complexes are not a routine consequence of injection therapy for allergic disease.

Adult↗

Intracortical distribution of number and volume of glomeruli during postnatal maturation in the dog.

Morphometric analysis was carried out on kidneys of neonatal dogs in which function of the entire kidney and of single nephrons had been evaluated. Measurements were begun after neogenesis of nephrons had been completed, i.e., at the end of the 3rd postnatal wk. They were continued to 74 days by which time glomerular function, expressed per unit of renal weight, had reached the mature level. For statistical analysis, the cortical histogram at each age was divided into eight zones of equal depth between the capsule and corticomedullary junction. The mean total number of glomeruli in this beagle strain was 589 x 10(3) per kidney. The fraction of the total number of glomeruli was lowest in the subcapsular layer (3.9%) and highest (24.5%) in the zone immediately beneath from where it decreased almost linearly to a value of 4.5% in the juxtamedullary region. This numerical distribution did not change with age, which suggests that growth of nonglomerular structures proceeded at the same rate in all cortical layers. Volume of the glomerular tuft rose slightly between the subcapsular and next layer and remained constant down to the juxtamedullary region where it increased sharply. The juxtamedullary glomerulus was about 45% larger in volume than the other glomeruli. This intracortical distribution of glomerular volume did not vary between 23 and 74 days, although the volume of an individual glomerulus at each level increased slightly with age. Total glomerular volume increased by 33% during the postnatal period studied, whereas simultaneously nonglomerular cortical volume rose by 235%. On the assumption that nonglomerular tissue consists mainly of tubules, the data suggest that the rate of tubular growth far exceeded that of glomerular growth. Despite this difference in glomerular and tubular growth rates, analysis of single nephrons in these dogs demonstrates constant and mature proximal fractional reabsorption of sodium and water.

Absorption↗